rs761510301

chr16-7653930-G-Achr16-7653930-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018723.4(RBFOX1):c.873G>A(p.Pro291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000767 in 1,551,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: RBFOX1 NM_018723.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

Genes affected

RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 16-7653930-G-A is Benign according to our data. Variant chr16-7653930-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 460035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS2: High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.873G>A	p.Pro291=	synonymous_variant	12/16	ENST00000550418.6
RBFOX1	NM_145893.3	c.933G>A	p.Pro311=	synonymous_variant	9/14	ENST00000355637.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.873G>A	p.Pro291=	synonymous_variant	12/16	1	NM_018723.4	A1
RBFOX1	ENST00000355637.9	c.933G>A	p.Pro311=	synonymous_variant	9/14	1	NM_145893.3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152108 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000538 AC: 9 AN: 167316 Hom.: 0 AF XY: 0.0000533 AC XY: 5 AN XY: 93746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000748

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000809

Gnomad OTH exome AF: 0.000239

GnomAD4 exome AF: 0.0000808 AC: 113 AN: 1399082 Hom.: 0 Cov.: 35 AF XY: 0.0000751 AC XY: 52 AN XY: 692388

Gnomad4 AFR exome AF: 0.0000316

Gnomad4 AMR exome AF: 0.0000264

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000236

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000802

Gnomad4 NFE exome AF: 0.0000901

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152108 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74314

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic generalized epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 19, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	7.0
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs761510301; hg19: chr16-7703932;